The roles of hormones and substrates in the regulation of blood glucose and amino acid metabolism will be examined in normal physiology and in diabetes mellitus. In insulin-dependent diabetics the effects of exercise on the mobilization of subcutaneously injected insulin and the effect of using non-exercised injection sites (e.g., the abdomen) on the hypoglycemic response to exercise will be examined. The relative importance of insulin lack and glucagon excess in the pathogenesis of diabetes will be evaluated by determining the effect of somatostatin on oral glucose ingestion in maturity onset diabetics. The effect of the route of glucose administration on hepatic versus peripheral (fat and muscle) uptake of glucose will be examined by studying dogs with chronically implanted portal venous, hepatic and arterial catheters. Glucose will be administered orally and via a peripheral or portal vein and net hepatic and peripheral uptake of glucose will be compared. In other studies the effect of prior exercise on hepatic versus peripheral glucose uptake will be determined. Finally, glucose-amino acid interactions will be examined by determining the effect of restriction of dietary carbohydrate on the amino acid response to a protein meal.